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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Blajchman, M. A. Articles by Schulman, S. Search for Related Content PubMed PubMed Citation Articles by Blajchman, M. A. Articles by Schulman, S. Related Collections Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Antithrombin-III-Stockholm: a codon 392 (Gly----Asp) mutation with normal heparin binding and impaired serine protease reactivity MA Blajchman, F Fernandez-Rachubinski, WP Sheffield, RC Austin and S Schulman Canadian Red Cross Blood Society Transfusion Service, Hamilton, Ontario. Antithrombin-III-Stockholm is a new structural variant of antithrombin- III (AT-III) with normal heparin affinity but defective serine protease inhibitory activity. The proposita, a white female born in 1966, was diagnosed to have developed a pulmonary embolus while on oral contraceptives at age 19. The proposita, as well as her father, were diagnosed to have a type 2 AT-III deficiency as they had normal levels of immunoreactive AT-III associated with decreased (approximately 60%) functional AT-III when measured with either alpha-thrombin or factor Xa as the substrate, either in the presence or absence of heparin. There was no evidence of abnormal electrophoretic mobility of AT-III from the proposita either in the presence or absence of heparin. Genomic DNA was prepared and all seven AT-III exons were polymerase chain reaction (PCR)-amplified and sequenced in both directions using nested primers. Only exon 7 provided evidence for the presence of a mutation, with the second base of codon 392 having a G----A substitution. Such a mutation would cause the substitution of aspartic acid at the site of the normally appearing glycine in the translated product. Furthermore, this mutation caused the destruction of an Hae III restriction site at this point in the AT-III gene. The absence of this Hae III site was confirmed using restriction fragment length polymorphism analysis of PCR-amplified material from the proposita. Experiments with AT-III from the proposita together with experiments with cell-free translated AT- III-Stockholm provided evidence that the mutant AT-III protein does not efficiently form a stable covalent inhibitory complex with alpha- thrombin, although it exhibits normal heparin affinity. The minimal thrombin-complexing ability of the mutant AT-III protein that was observed was accelerated by heparin, but to subnormal levels. Volume 79, Issue 6, pp. 1428-1434, 03/15/1992 Copyright © 1992 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Discrepancy between antithrombin activity methods revealed in Antithrombin Stockholm: do factor Xa-based methods overestimate antithrombin activity in some patients? Johanna S. Ungerstedt, Sam Schulman, Nils Egberg, Jovan Antovic, and Margareta Blombäck Blood 2002 99: 2271-2272. [Full Text] [PDF] This article has been cited by other articles: J. S. Ungerstedt, S. Schulman, N. Egberg, J. Antovic, and M. Blomback Discrepancy between antithrombin activity methods revealed in Antithrombin Stockholm: do factor Xa-based methods overestimate antithrombin activity in some patients? Blood, March 15, 2002; 99(6): 2271 - 2272. [Full Text] [PDF]

	Copyright © 1992 by American Society of Hematology         Online ISSN: 1528-0020